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Biomedical subjects

F Larrea

Publications and source records attributed to F Larrea.

At least 55 records · Page 3Linked to original sources

Heterogeneity of serum prolactin throughout the menstrual cycle and pregnancy in hyperprolactinemic women with normal ovarian function.

We have demonstrated the selective secretion of high mol wt PRL series (big big PRL) in women with hyperprolactinemia and normal ovarian function. This observation suggests that big big PRL is immunologically similar, but biologically less active, than monomeric or little PRL. In this study we determined the molecular size heterogeneity of immunoreactive PRL in the serum from two ovulatory hyperprolactinemic women (subjects A and B) who had large amounts of serum big big PRL during a menstrual cycle and/or gestation. Serum samples obtained throughout the menstrual cycle (days 6, 10, 14, 17, 23, and 28, taking as day 1 the first day of bleeding) and pregnancy (weeks 7, 9, 11, 15, 20, 25, 30, 34, and 38) were fractionated by gel filtration chromatography. PRL was identified in column eluates by specific RIA. Two additional pregnant women, one with a bromocriptine-treated PRL-secreting adenoma (subject C), and a normal woman (subject D) were studied. Big big PRL was the predominant species throughout the different phases of the menstrual cycle in subject B, comprising 70-80% of the total immunoreactive PRL. Most of the remainder was big PRL, and little PRL was present in only small amounts (6-12%) during the luteal phase. During their pregnancies, the serum PRL in subjects A and B initially was mostly big big PRL, but later in gestation the PRL composition shifted from the high mol wt variants to little PRL. The infant's cord (subject A) and peripheral (subject B) serum at birth contained appreciable quantities of big big and big PRL, respectively. These results indicate that structural changes in PRL occur during pregnancy and the menstrual cycle which are probably influenced by the hormonal environment. In addition, the occurrence of larger mol wt PRL species in the serum of the infant of a hyperprolactinemic mother suggests that the presence of high proportions of big big PRL in the serum is genetically determined.

Adult↗

Studies on the microheterogeneity of anterior pituitary follicle-stimulating hormone in the female rat. Isoelectric focusing pattern throughout the estrous cycle.

Anterior pituitary (AP) glands were removed from adult female rats at different times throughout the estrous cycle, and the isohormones of follicle-stimulating hormone (FSH) present within them were separated by isoelectric focusing in polyacrylamide gels (PAGE-IEF; pH range 3.0-8.0). Gel eluents were analyzed for FSH content by radioimmunoassay (RIA) and radioreceptor assay (RRA). All AP samples exhibited several peaks of FSH immunoactivity within a pH range of 6.2-4.0; the major peak constantly exhibited an isoelectric point (pI) of 4.9-4.5. To quantify differences in the IEF pattern of AP-FSH between the pituitaries collected during the different days of the cycle, each PAGE-IEF profile was divided into 7 regions (pI 7.0-6.3 = Area 1, 6.2-5.5 = Area 2, 5.4-5.0 = Area 3, 4.9-4.5 = Area 4, 4.4-4.0 = Area 5, 3.9-3.5 = Area 6, and less than 3.5 = Area 7), and the amount of FSH present within each was determined. In all APs collected at 0900 h of diestrus 1 (D1) and 2 (D2), proestrus (P), and estrus (E); at 1300 h of D1, D2 and E; at 2200 h of P; and at 0200 h of E, the majority of FSH immunoactivity (37-55% of total FSH on gel) focused within Area 4, whereas Areas 2 and 3 contained minor amounts of FSH activity (11-26% and 14-24%, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

The metabolism of 19-nor contraceptive progestins modulates their biological activity at the neuroendocrine level.

In this communication, a series of studies from our laboratory dealing with the mechanism of action of 17 alpha-ethinyl derivatives of 19-nor testosterone are reviewed. The administration of norethisterone (NET) to long-term castrated female rats induces the nuclear translocation of pituitary estradiol receptors and is followed by some estrogenic-like effects at the hypothalamic-pituitary unit. It is established that an A-ring reduced metabolite of NET, the 3 beta,5 alpha-tetrahydro NET derivative, is responsible for the observed in vivo estrogenic effects of the parent compound. 3 beta,5 alpha-NET binds to the estrogen receptor and is efficient in inducing the pituitary estrogen-dependent progesterone receptor and in increasing the uterine weight in long-term castrated rats. Furthermore, administration of 3 beta,5 alpha-NET and the 5 alpha-reduced metabolite of NET (5 alpha-NET) are able to inhibit the release of gonadotropins in the castrated animal to a greater extent than NET. Moreover, pretreatment with tamoxifen, an estrogen binding site competitor, results in a significant diminution of the antigonadotropic potency of 3 beta,5 alpha-NET but not of the 5 alpha-NET, which is only inhibited by the administration of cyproterone acetate. These findings underline the importance of the metabolic rate of NET for the expression of its biological effects at the hypothalamic-pituitary unit.

Animals↗

[Non-Hodgkin's lymphoma as a cause of intussusception in children].

From 1972 to 1985, a total of 35 children with histological diagnosis of non-Hodgkin's lymphoma were treated. A previously undiagnosed abdominal non-Hodgkin's lymphoma produced intussusception in three of these children between 5 and 10 years of age. Our experience indicates that any child around 6 years of age with abdominal pain, bloody stools and a palpable mass plus radiographic evidence of intussusception should be considered to have an intestinal wall lymphoma until proven otherwise. Inadequate surgical treatment may result from failure to recognize relationship between intussusception and lymphoma in older child.

Child↗

Familial occurrence of big-big prolactin as the predominant immunoreactive human prolactin species in blood.

The occurrence of big-big prolactin (PRL) as the major form of circulating immunoactive PRL has been described in ovulatory hyperprolactinemia. In this study, we have analyzed the heterogeneity of circulating human PRL in 17 members of three families in which one member, bearing galactorrhea-hyperprolactinemic syndrome, was known to have serum big-big PRL as the predominant circulating species. Gel filtration patterns of serum samples of all subjects revealed the presence of significant proportions of big-big PRL in more than one member of the same family, thus suggesting the familial occurrence of big-big as the predominant immunoreactive PRL species in blood.

Adult↗

T-cell dysregulation in patients with hyperprolactinemia: effect of bromocriptine treatment.

We studied four patients with tumoral hyperprolactinemia and normal ovarian function before and after prolactine levels had become normal with treatment with bromocriptine (BrC), a dopamine agonist that inhibits prolactin release. Their proliferative responses to concanavalin A, pokeweed mitogen, and, to a lesser extent, phytohemagglutinin, their spontaneous and concanavalin A-induced suppression, and their production of interleukin 2 were found to be decreased and to correct partially or completely after bromocriptine treatment. The T-cell response to interleukin 2 was low in two patients in whom it increased after BrC treatment. These findings give insight on the immunomodulatory role of prolactin in vivo.

Adult↗

Induced hyperprolactinaemia does not alter FSH binding or ABP secretion in the rat testis.

The effects of induced hyperprolactinaemia in male Wistar rats were studied by grafting two pituitary glands under the kidney capsule. Transplants were performed at 15 and 60 days of age, and rats killed 4 weeks later when tissue and serum samples were obtained. Serum concentrations of LH were reduced significantly in rats grafted at 60 days of age, whereas no change was observed in rats grafted at 15 days of age. Serum testosterone levels were slightly suppressed only in the older group of grafted rats. Testicular FSH receptors and the epididymal content of androgen-binding protein (ABP) were not modified by induction of hyperprolactinaemia. The results indicate that hyperprolactinaemia was not associated with changes in at least two functional parameters of the tubular compartment of the rat testis.

Androgen-Binding Protein↗

Microheterogeneity of anterior pituitary FSH in the male rat: isoelectric focusing pattern throughout sexual maturation.

Anterior pituitary glands were removed from male rats at 5, 10, 15, 18, 21, 28, 30, 40, 50 and 90 days of age, and the multiple forms of FSH present within them were separated by polyacrylamide gel-isoelectric focusing (PAGE-IEF; pH range 3.0-8.0). Gel eluents were analysed for FSH content by radioimmunoassay (RIA) and a specific radioreceptor assay (RRA). All pituitaries studied exhibited one or more peaks of immunoactive FSH within a pH range of 7.0-3.0; the major peak exhibited an isoelectric point (pI) of 4.9-4.0. Between 25 and 56% of anterior pituitary FSH obtained from rats 5-30 days old focused within a pH range of 4.9-4.5, whilst in older animals (greater than or equal to 40 days) this pH range contained 17-27% of the total FSH recovered. In contrast, in animals 40-90 days old, the greatest proportion of immunoactive FSH (42-62% of the total immunoactivity recovered) focused within a pH range of 4.4-4.0; further, only these groups of animals exhibited a significant proportion of anterior pituitary FSH with a pI less than or equal to 3.9. Between 14 and 21% of total FSH from 5- to 30-day-old rats focused within a pH range of 5.4-5.0, whereas in older animals this pH range contained 6-9% of the total FSH recovered. These shifts in FSH pI occurred at the time of appearance of spermiogenesis, at 45 days of age. Although the ratio of the concentration of FSH measured by RRA to that measured by RIA declined as the pI of the anterior pituitary FSH decreased throughout a pH range of 7.0-4.0, the most acidic FSH molecules (pI less than 4.0) showed an abrupt increase in that ratio. These results demonstrate that the transition from sexual immaturity to adulthood is accompanied by qualitative changes of intracellular pituitary FSH. They contrast with previous findings in female rats in which a shift to less acidic anterior pituitary FSH forms was detected at the time of vaginal opening, thus indicating the existence of a sexual dichotomy in terms of the action of gonadal steroids on the type of FSH molecule synthesized by the anterior pituitary gland.

Animals↗

Transient idiopathic subpleural cysts in the newborn: an observation in two patients.

We present two cases of transient idiopathic cystic formations in the subpleural region in full-term newborns, that do not fit into any known cystic process to our knowledge. The features of the cystic formations, their subpleural location, their spontaneous regression, the histopathological study, as well as the absence of a clear etiology, have led us to propose the name of "Transient Idiopathic Subpleural Cysts in Full-term Newborns", for this process.

Cysts↗

Effects of oestradiol-17 beta and LRH upon the two fractions of pituitary follicle-stimulating hormone separated by concanavalin-A chromatography.

The effects of oestradiol-17 beta (E2) and LRH upon the two fractions of pituitary follicle stimulating hormone (FSH) obtained by concanavalin A (Con A) chromatography were studied. Anterior pituitary glands were removed from adult intact rats at different times throughout the oestrous cycle, and from long-term ovariectomized (Ovx) rats after specific endocrine treatments. The presence, relative ratio and biological activity of each Con A separable FSH fraction were assessed by a specific radioimmunoassay and by an in vitro bioassay. After separation by concanavalin A chromatography, glands from intact rats sacrificed during the days of oestrus, dioestrus 1 and dioestrus 2, exhibited constant relative ratios (U:B FSH ratio) of the two FSH fractions so separated (Con A unbound and bound FSH), whereas donors sacrificed at the morning and early afternoon (13.00-15.00 h) of the day of pro-oestrus, showed the highest U:B FSH ratio; this ratio abruptly declined at the time of the FSH surge, after 15.00 h of pro-oestrus. Ovx rats exhibited lower ratios than intact animals. Pituitary extracts from Ovx donors under short-term (20 h) E2 exposure (condition which decreased pituitary sensitivity to LRH), showed the lowest U:B FSH ratio, whereas glands from Ovx rats exposed to conditions which caused increased pituitary LRH exposure (immediately before the oestradiol-induced FSH surge or after injection of 100 ng of LRH) showed an increase in their U:B FSH ratio, as compared with Ovx and Ovx + E2 (20 h) rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Further evidence that big,big prolactin is preferentially secreted in women with hyperprolactinemia and normal ovarian function.

The heterogeneity of human serum prolactin (PRL) in 12 women with hyperprolactinemia and different derangements of the hypothalamic-pituitary-ovarian axis was studied. The patients were subdivided into three groups: four women with hyperprolactinemia and normal ovarian function (group I), four women with hyperprolactinemia associated with sporadic endometrial bleedings and a positive progestin test (group II), and four women with amenorrhea and a negative progestin test (group III). Gel filtration chromatography of serum samples from patients in group I revealed in three of them that most (80%) of their immunoreactive PRL eluted as big,big PRL (Mr greater than 100,000); whereas the rest of the patients, including those from groups II and III, exhibited a distribution pattern similar to that obtained in normal menstruating women. All PRL species had similar affinities for the antibody, as disclosed by the slopes generated in dose-response curves. These results indicate that ovarian function in hyperprolactinemia might be dependent upon PRL heterogeneity and suggest that big,big PRL may have, under in vivo conditions, a low degree of biologic activity.

Adult↗

Estrogen-like effects of norethisterone on the hypothalamic pituitary unit of ovariectomized rats.

The acute and chronic effects of norethisterone (NET) upon gonadotropin dynamics were studied in long-term ovariectomized adult Wistar rats. Time course studies showed that plasma LH declined within 1 h following a single NET sc injection and remained low for the next 4 h duration of the experiment. Pre-treatment with tamoxifen prevented the acute anti-gonadotropic effect of NET and GnRH administration to NET treated rats resulted in an abolishment of the pituitary responsiveness in terms of LH. Chronic administration of NET but not progesterone to castrated animals induced a significant decrease of plasma and pituitary LH with a concomitant replenishment of hypothalamic GnRH in an identical fashion to that observed with chronic administration of 17 beta-estradiol. Furthermore, administration of NET and 17 beta-estradiol but not progesterone diminished the number of GnRH pituitary binding sites to levels found prior castration. These results indicate that the effects of this 19-nor synthetic progestin upon gonadotropin modulation in the long-term gonadectomized rat do not resemble those of progesterone and suggest that NET is acting through different mechanisms. The data are consistent with an estrogen-like mode of action.

Animals↗

Interaction of medroxyprogesterone acetate with cytosol androgen receptors in the rat hypothalamus and pituitary.

The binding of medroxyprogesterone acetate (MPA) with cytosol androgen receptors from rat pituitary and hypothalamus was studied. The pituitary and hypothalamic cytosol androgen receptors from adult castrated female rats were in vitro labeled using 3H natural (testosterone (T) and 5 alpha-dihydrotestosterone (DHT] and [3H]synthetic (methyltrienolone) androgens as radioligands. The [3H]androgen-receptor complexes sedimented with a coefficient of 8S in linear sucrose gradients. When incubated with an excess of radioinert MPA, specific binding was abolished indicating interaction of MPA with androgen receptors. Furthermore specific [3H]MPA-androgen cytosol receptor complexes could be identified in these neuroendocrine tissues when a post-gradient receptor labeling technique was used in the absence or presence of radioinert MPA, DHT, and triamcinolone acetonide. A study of binding kinetics disclosed that the equilibrium dissociation constant and saturation binding capacity for the MPA binder, were similar to those exhibited by DHT binding to androgen receptors in both studied tissues under identical experimental conditions. The overall results were interpreted as demonstrating that MPA interacts with cytosol steroid receptors other than those of progesterone in the rat hypothalamus and anterior pituitary. The data are consistent with MPA binding to androgen receptors.

Animals↗

Nuclear translocation of estradiol receptors by the in vivo administration of norethisterone: an alternate mechanism for gonadotropin inhibition.

In order to investigate the anti-gonadotropic effect of norethisterone (NET) in long-term ovariectomized rats, we studied the interaction of this synthetic progestin with intracellular steroid receptors in the anterior pituitary by a nuclear exchange assay. The results demonstrated that the administration of NET to long-term ovariectomized rats resulted in nuclear translocation of estradiol cytosol receptors in the pituitary and uterus with a rate of accumulation and nuclear retention being similar in both tissues. Accumulation of nuclear estradiol receptors in the pituitary was in agreement with the rate of LH inhibition in NET-treated rats. The results presented in this communication may explain the anti-gonadotropic activity of NET in long-term ovariectomized rats in addition to its well known progestational activity.

Animals↗

Hypergonadotrophic hypogonadism in an XX female subject due to 17,20 steroid desmolase deficiency.

A 22 year old XX female patient with primary amenorrhoea and sexual infantilism was studied. Persistently elevated serum LH and FSH concentrations and exaggerated LRH pituitary responsiveness indicated deficient ovarian hormonal production. Serum levels of C21 and C19 steroids measured by specific radioimmunoassays before and after appropriate stimulations demonstrated an impairment of adrenal and ovarian steroid biosynthesis. Baseline levels of androstenedione (delta 4-A), testosterone (T), and oestradiol-17 beta (E2) were persistently below the normal range for healthy women at early follicular phase, whereas progesterone (P) and 17 alpha-OH-progesterone (17-OH-P) serum levels were significantly higher than those observed for normal women. Adrenal and gonadal stimulation with ATCH and hCG, respectively, resulted in a considerable rise in serum P and 17-OH-P without any significant change in circulating levels of delta 4-A, T, and E2. These findings were consistent with the diagnosis of 17,20 steroid desmolase deficiency at both adrenal and ovarian levels. This is the first report of a 17,20 desmolase deficiency in an XX individual, and is in line with previous suggestions that familial occurrence of the disorder would fit an autosomal recessive pattern of inheritance.

Adrenal Cortex Hormones↗

Origin of the heavy and light protomers of androgen-binding protein from the rat testis.

Androgen-binding protein (ABP) isolated from rat epididymides by androgen affinity chromatography is a dimer with a native molecular weight of 85,000. When fractionated on sodium dodecyl sulfate gels two components were identified which were present in a 3:1 ratio; these were designated heavy (H) and light (L) (Mr of 45,000 and 41,000), respectively. The fact that H and L both have steroid binding sites and that they can be cross-linked suggests that both are protomers of native ABP. NH2-terminal analysis, amino acid analysis, and peptide maps suggest an extensive homology between H and L. In addition, peptide maps of H and L photolabeled with delta 6-[3H]testosterone suggest that the binding sites on these protomers are identical. ABP was also purified 33,800-fold from testes. The H and L protomers from this preparation were identical with those from the epididymides as judged by peptide maps. In addition, [35S]methionine was incorporated into the H and L synthesized by Sertoli cells in the same 3:1 ratio as in highly purified ABP from testis and epididymis. These observations suggest that L is not derived from H following secretion. Selective incorporation of [3H] fucose into the H protomer suggests that differences in carbohydrate composition account for at least part of the difference between H and L. These results support the conclusion that native ABP is composed of two kinds of protomers which exist in a ratio of 3:1. These protomers are similar polypeptides that differ partly in carbohydrate composition.

Androgen-Binding Protein↗